Magnesium sulfate has sex-specific, dose-dependent vasodilator effects on preterm placental vessels

Background Women at risk of preterm delivery receive magnesium sulfate (MgSO 4 ) in the pre-delivery phase to reduce their child\u27s risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain. Methods The aim of this study was to examine MgSO 4 action on vascular tone in male and female human placental vessels from term and preterm deliveries. Vessels were obtained from placental biopsy following birth at term (37-41 weeks) or preterm gestation (gestation). The vessels were mounted on a pressure myograph, pre-constricted with synthetic endoperoxide prostaglandin PGH 2 (U46619) (0.1-100 μmol/l), and percentage of relaxation was calculated following incubation with bradykinin. Experiments were carried out in the presence of MgSO 4 (0.2 mmol/l), N Ψ -nitro-L-arginine methyl ester (L-NAME) (0.1 mmol/l), indomethacin (10 μmol/l), Ca 2+ -activated K + channel blocker TRAM-34 (1 μM) and apamin (3 μM) to assess mechanisms of vascular function. Vascular [calcium ions (Ca 2+ )] was analysed using a colorimetric calcium assay. Results Vasodilation in vessels from preterm males was significantly blunted in the presence of MgSO 4 when compared to preterm female and term male and female vessels. Overall, MgSO 4 was observed to differentially modulate placental vascular tone and vascular calcium concentrations in a sex-specific manner. Conclusions As MgSO 4 regulates human placental blood flow via specific pathways, foetal sex-specific MgSO 4 treatment regimes may be necessary. In an era of increasing awareness of individualised medicine, sex-specific effects may be of importance when developing strategies to optimise care in high-risk patients

The Dominion Range Ice Core, Queen Maud Mountains, Antarctica - General Site and Core Characteristics with Implications

The Transantarctic Mountains of East Antarctica provide a new milieu for retrieval of ice-core records. We report here on the initial findings from the first of these records, the Dominion Range ice-core record. Sites such as the Dominion Range are valuable for the recovery of records detailing climate change, volcanic activity, and changes in the chemistry of the atmosphere. The unique geographic location of this site and a relatively low accumulation rate combine to provide a relatively long record of change for this potentially sensitive climatic region. As such, information concerning the site and general core characteristics are presented, including ice surface, ice thickness, bore-hole temperature, mean annual net accumulation, crystal size, crystal fabric, oxygen-isotope composition, and examples of ice chemistry and isotopic composition of trapped gases

Ice-core Records and Ozone Depletion—Potential for a Proxy Ozone Record

Time-series of the ionic composition in polar ice cores can provide detailed direct and proxy records of seasonal to Millenial scale fluctuations in climate, atmospheric chemistry, and volcanic activity. Even though problems of species-source links and air/snow fractionation have not all been entirely resolved,the fact remains that ice cores currently hold the best hope of retrieving detailed paleo-atmospheric records. While direct links between the chemistry in ice cores and the ozone depletion phenomenon cannot be guaranteed, ice-core records provide the only means by which signals related to the ozone cycle can be produced for pre-measurement periods or for unmonitored sites. We propose that measurements of nitrate and/or chloride in polar snow/ice samples may provide proxy records of ozone depletion because of the role these species play in the ozone cycle (e.g., see summary review by Schoeberl and Krueger 1986). Heterogeneous chemical reactions in the ant-arctic atmosphere involving catalyzing agents such as chlorine monoxide, bromine monoxide, and/or nitrogen oxides are known to be effective in reducing ozone concentrations through their effect on the general reaction: oxygen plus ozone forms 202(e.g., McElroy et al. 1986a). Removal of nitrogen oxides by condensation from polar stratospheric clouds (e.g., Toon et al.1986; McElroy et al. 1986b; Crutzen and Arnold 1986) triggered particularly by cooling in the stratosphere helps set the stage for more efficient removal of ozone by reactions with chlorine monoxide and bromine monoxide (e.g., McElroy et al. 1986a). These reactions may result in increased concentrations of nitrate and chloride in polar snow/ice cores

Augmented cardiac growth hormone signaling contributes to cardiomyopathy following genetic disruption of the cardiomyocyte circadian clock

Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH sensitivity in target tissues. GH acts in part through induction of insulin-like growth factor 1 (IGF1), and excess GH/IGF1 signaling has been linked to pathologies such as insulin resistance, acromegaly, and cardiomyopathy. Interestingly, genetic disruption of the cardiomyocyte circadian clock leads to cardiac adverse remodeling, contractile dysfunction, and reduced lifespan. These observations led to the hypothesis that the cardiomyopathy observed following cardiomyocyte circadian clock disruption may be secondary to chronic activation of cardiac GH/IGF1 signaling. Here, we report that cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit increased cardiac GH sensitivity, as evidenced by augmented GH-induced STAT5 phosphorylation (relative to littermate controls) in the heart (but not in the liver). Moreover

Financial management practice amongst SMEs

While deficiencies in financial management have been repeatedly cited as a root cause of business failure (Najak and Greenfield 1994) two arguments are advanced for such deficiencies in SMEs; that new accounting is not relevant and that SME managers are unable to make use of accounting. Here it is argued that accounting ideas are relevant to SMEs but that a process of innovation combining both knowledge to overcome a barrier of belief and an external shock are necessary in order for innovation to take place. These ideas were explored through a survey of SMEs from both service and manufacturing business in the Greater Manchester region. It was observed that the use of accounting techniques is negatively related to growth in turnover. However the use of accounting techniques that were related to product market was found to be positively related to growth in turnover and that owner/managers belief in the importance of accounting in business decisions was strongly related to growth in turnover. These results were the more interesting when it was observed that growth was negatively related to size. A second theme of the research was the significance of the role of external advisors. Prima facie it was suggested that external advisors may be key agents of change, but the study found that their (accountants, academics and consultants) perceived value was relatively low. The findings of this survey suggest that when accounting is perceived to be relevant then its use does support business growth but innovation in accounting in SME requires further research

Amonafide: An active agent in the treatment of previously untreated advanced breast cancer--a cancer and leukemia group B study (CALGB 8642)

Amonafide is a new imide derivative of naphthalic acid. The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials. The drug is extensively metabolized and detected in plasma and urine. Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CALGB) master metastatic breast cancer protocol. CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil, or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed. Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis. Amonafide was given at 300 mg/m2/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles. Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof. Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia. The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = \u3c0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response. Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) with amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping

Nitrous oxide improves cardiovascular, respiratory, and thermal stability during prolonged isoflurane anesthesia in juvenile guinea pigs

Anesthesia is frequently used to facilitate physiological monitoring during interventional animal studies. However, its use may induce cardiovascular (central and peripheral), respiratory, and thermoregulatory depression, confounding results in anesthetized animals. Despite the wide utility of guinea pigs as a translational platform, anesthetic protocols remain unstandardized for extended physiological studies in this species. Therefore, optimizing an anesthetic protocol that balances stable anesthesia with intact cardiorespiratory and metabolic function is crucial. To achieve this, 12 age and sex-matched juvenile Dunkin Hartley guinea pigs underwent extended anesthesia (≤150 min) with either (a) isoflurane (ISO: 1.5%), or (b) isoflurane + N2O (ISO+ N2O: 0.8% +70%), in this randomized cross-over designed study. Cardiovascular (HR, SBP, peripheral microvascular blood flow), respiratory (respiratory rate, SpO2), and thermal (Tre and Tsk) measures were recorded continuously throughout anesthesia. Blood gas measures pre- and post- anesthesia were performed. Incorporation of 70% N2O allowed for significant reductions in isoflurane (to 0.8%) while maintaining an effective anesthetic depth for prolonged noninvasive physiological examination in guinea pigs. ISO+N2O maintained heart rate, peripheral blood flow, respiratory rate, and thermoregulatory function at levels closest to those of conscious animals, especially in females; however, it did not fully rescue anesthesia-induced hypotension. These results suggest that for studies requiring prolonged physiological examination (≤150 min) in guinea pigs, 0.8% isoflurane with a 70% N2O adjuvant provides adequate anesthesia, while minimizing associated cardiorespiratory depression. The preservation of cardiorespiratory status is most marked throughout the first hour of anesthesia

Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience

Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH ≥ Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation

Global trends and patterns of commercial milk-based formula sales:is an unprecedented infant and young child feeding transition underway?

OBJECTIVE: The marketing of infant/child milk-based formulas (MF) contributes to suboptimal breast-feeding and adversely affects child and maternal health outcomes globally. However, little is known about recent changes in MF markets. The present study describes contemporary trends and patterns of MF sales at the global, regional and country levels. DESIGN: Descriptive statistics of trends and patterns in MF sales volume per infant/child for the years 2008-2013 and projections to 2018, using industry-sourced data. SETTING: Eighty countries categorized by country income bracket, for developing countries by region, and in countries with the largest infant/child populations. SUBJECTS: MF categories included total (for ages 0-36 months), infant (0-6 months), follow-up (7-12 months), toddler (13-36 months) and special (0-6 months). RESULTS: In 2008-2013 world total MF sales grew by 40·8 % from 5·5 to 7·8 kg per infant/child/year, a figure predicted to increase to 10·8 kg by 2018. Growth was most rapid in East Asia particularly in China, Indonesia, Thailand and Vietnam and was led by the infant and follow-up formula categories. Sales volume per infant/child was positively associated with country income level although with wide variability between countries. CONCLUSIONS: A global infant and young child feeding (IYCF) transition towards diets higher in MF is underway and is expected to continue apace. The observed increase in MF sales raises serious concern for global child and maternal health, particularly in East Asia, and calls into question the efficacy of current regulatory regimes designed to protect and promote optimal IYCF. The observed changes have not been captured by existing IYCF monitoring systems

Assessing a New Clue to How Much Carbon Plants Take Up

Current climate models disagree on how much carbon dioxide land ecosystems take up for photosynthesis. Tracking the stronger carbonyl sulfide signal could help